Cilostazol is known by the chemical name 6-[4-(1-Cyclohexyl-1H-tetrazol-5-yl)butoxy]-3,4-dihydro-2(1H)-quinolinone. It is marketed under the tradename PLETAL® (Otsuka America Pharmaceutical, Inc.) in the United States for the treatment of intermittent claudication and under the tradename PLETAL® in Japan and South Korea for the treatment of chronic arterial occlusive disease, including diabetic complications of the peripheral vasculature. Cilostazol is also approved in Europe. The recommended daily dose is 100 mg BID, with 50 mg BID recommended if co-administering strong inhibitors of CYP3A4 and CYP2C19.
Cilostazol is a selective inhibitor of phosphodiesterase III with antiplatelet and antithrombotic activity. More specifically, cilostazol and several of its metabolites are cyclic AMP (cAMP) phosphodiesterase III inhibitors (PDE III inhibitors), inhibiting phosphodiesterase activity and suppressing cAMP degradation. This action results in an increase in cAMP in platelets and blood vessels, leading to inhibition of platelet aggregation and vasodilation, respectively. For example, cilostazol reversibly inhibits platelet aggregation induced by a variety of stimuli, including thrombin, ADP, collagen, arachidonic acid, epinephrine, and shear stress.
Currently, there are fifteen ongoing clinical trials for cilostazol in the areas of cerebral infarction, cerebrovascular disorders, atherosclerosis, diabetes mellitus complications, peripheral vascular disease, Reynaud's disease, intermittent claudication, ischemic heart disease, and acute coronary syndrome.
Additional trials are investigating cilostazol in combination with other therapeutics. For example, trials are investigating cilostazol in combination with aspirin in ischemic stroke patients (“Overcome Biochemical Aspirin Resistane [sic] Through Cilostazol Combination (ARCC)”) and in combination with aspirin in chronic stroke patients studying the effect of aspirin plus cilostazol and aspirin alone on the progression of intracranial arterial stenosis, in 200 chronic stroke patients with 50-99% stenosis.
Despite the beneficial activities of cilostazol, there is a continuing need for new compounds to treat the aforementioned diseases and conditions.